Targeting exon 20 insertion mutations in lung cancer

by Selleckchem | Jan 14 2024

Purpose of review: The application of tyrosine kinase inhibitor (TKI) has successfully changed the standard of care in epidermal growth factor receptor ( EGFR ) positive non-small cell lung cancer. However, clinical survivals for patients with EGFR exon 20 insertions have failed to improve over the long period and the mutation appeared resistant to EGFR -TKIs. This overview focused on the current treatment strategies, summarized the emerging regimens for patients with EGFR exon 20 insertions, and demonstrated historical challenges and future development.

Recent finding: Current clinical trials suggested that several regimens selectively-targeted EGFR exon 20 insertions presented potent antitumor activity, like mobocertinib and the bispecific anti- EGFR-MET monoclonal antibody amivantamab and were approved by Food and Drug Administration (FDA) in patients progressed beyond first-line treatment. Novel treatments, including DZD9008, CLN-081, revealed modest clinical efficacy as well and clinical trials are underway, which may lead to improvement of survival outcomes.

Summary: Recent clinical evidence indicates that targeted therapies could improve survival benefits to some extent. More efforts on drug development are underway to bring higher response rates both extracranial and intracranial, sustained clinical remission, and better survival benefits.

Comments:

It sounds like your review is addressing a critical aspect of lung cancer treatment—specifically focusing on EGFR-positive non-small cell lung cancer (NSCLC) and the challenges posed by EGFR exon 20 insertions. The emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs) in this context and the need for alternative treatment strategies are key points you've highlighted.

The overview discusses recent advancements, notably the emergence of promising treatments like mobocertinib, amivantamab, DZD9008, and CLN-081, which have shown efficacy in targeting EGFR exon 20 insertions. The FDA approval of mobocertinib and amivantamab for patients who have progressed beyond first-line treatment underscores the significance of these treatments in clinical practice.

Your summary rightly emphasizes the potential of targeted therapies in improving survival benefits, albeit with modest clinical efficacy in some cases. The ongoing efforts in drug development, reflected in clinical trials with novel treatments like DZD9008 and CLN-081, suggest a promising direction for enhancing treatment outcomes for patients with EGFR exon 20 insertions.

It seems your review provides a comprehensive view of the current landscape, highlights recent advancements, acknowledges the challenges faced historically, and points toward future developments that may offer improved survival outcomes. Are you looking to delve deeper into any specific aspect or need assistance with further details on any of these treatments or ongoing trials?